TY - JOUR
T1 - Local VEGF activity but not VEGF expression is tightly regulated during diabetic nephropathy in man
AU - Hohenstein, B.
AU - Hausknecht, B.
AU - Boehmer, K.
AU - Riess, R.
AU - Brekken, R. A.
AU - Hugo, C. P M
N1 - Funding Information:
The skilled technical assistance of Susanne Weber is gratefully acknowledged. This study was supported by a grant from the Deutsche Forschungsgemeinschaft to Dr Ch Hugo (SFB423 TP B6).
PY - 2006/5
Y1 - 2006/5
N2 - Several studies have implicated the angiogenic cytokine vascular endothelial growth factor (VEGF) in the development of diabetic nephropathy, but no data are available about its local activity during human disease. Glomeruli from 52 archival biopsies from type II diabetics were evaluated and compared to 10 renal biopsies without kidney disease (controls). Glomerulosclerosis, capillary rarefaction, glomerular and endothelial cell proliferation, apoptosis, VEGF expression, as well as receptor-bound VEGF indicating local VEGF activity, and phosphorylation of the signal transduction molecule Akt were investigated. Owing to substantial heterogeneity of glomerular lesions in individual biopsies, these parameters were correlated with the degree of injury in individual glomeruli rather than biopsies. Severe glomerular capillary rarefaction was linked to the degree of glomerulosclerosis. While cellular apoptosis was detected independent of the stage of injury, endothelial cell proliferation indicating capillary repair was markedly increased only in mildly/moderately injured glomeruli. In controls, VEGF was predominantly expressed in podocytes, whereas receptor-bound VEGF was confined to the glomerular endothelium. VEGF expression was increased in all diabetic glomeruli by many different cell types. In contrast, VEGF receptor activation was increased predominantly in the endothelium of only mildly injured glomeruli, but significantly decreased in more severely injured glomeruli. Diabetic nephropathy is associated with glomerular capillary rarefaction. Despite overall increased glomerular VEGF, the decreased receptor-bound VEGF on the endothelium may be an indicator of an insufficient capillary repair reaction.
AB - Several studies have implicated the angiogenic cytokine vascular endothelial growth factor (VEGF) in the development of diabetic nephropathy, but no data are available about its local activity during human disease. Glomeruli from 52 archival biopsies from type II diabetics were evaluated and compared to 10 renal biopsies without kidney disease (controls). Glomerulosclerosis, capillary rarefaction, glomerular and endothelial cell proliferation, apoptosis, VEGF expression, as well as receptor-bound VEGF indicating local VEGF activity, and phosphorylation of the signal transduction molecule Akt were investigated. Owing to substantial heterogeneity of glomerular lesions in individual biopsies, these parameters were correlated with the degree of injury in individual glomeruli rather than biopsies. Severe glomerular capillary rarefaction was linked to the degree of glomerulosclerosis. While cellular apoptosis was detected independent of the stage of injury, endothelial cell proliferation indicating capillary repair was markedly increased only in mildly/moderately injured glomeruli. In controls, VEGF was predominantly expressed in podocytes, whereas receptor-bound VEGF was confined to the glomerular endothelium. VEGF expression was increased in all diabetic glomeruli by many different cell types. In contrast, VEGF receptor activation was increased predominantly in the endothelium of only mildly injured glomeruli, but significantly decreased in more severely injured glomeruli. Diabetic nephropathy is associated with glomerular capillary rarefaction. Despite overall increased glomerular VEGF, the decreased receptor-bound VEGF on the endothelium may be an indicator of an insufficient capillary repair reaction.
KW - Diabetes
KW - Endothelial cell repair
KW - Receptor-bound VEGF
KW - VEGF
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U2 - 10.1038/sj.ki.5000294
DO - 10.1038/sj.ki.5000294
M3 - Article
C2 - 16541023
AN - SCOPUS:33646501496
SN - 0085-2538
VL - 69
SP - 1654
EP - 1661
JO - Kidney international
JF - Kidney international
IS - 9
ER -